Radiation therapy (radiotherapy) is well-established in the treatment of cancers. Such radiation generally involves the localized delivery of radiation to the site of a tumor, wherein such radiation is generally in the form of X-rays, beta particles (β−, i.e., electrons), gamma radiation (γ), and/or alpha particles (α, i.e., helium nuclei). Such radiation therapy relies on the free radical disruption of cellular DNA to destroy cancer cells in a targeted manner. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Such internal radiation therapy (localized or systemic) typically involves a careful selection of material comprising radioactive isotopes (radioisotopes) capable of delivering the desired type and amount of radiation.
Radioisotopes also find use as medical diagnostic tools. An example of this is in positron emission tomography (PET), wherein radioisotopes capable of emitting positrons (β+) find application. Other radioisotope-based diagnostic tools include gamma cameras and single photon emission computer tomography (SPECT). With the increasing use of radiopharmaceuticals with specific biological affinities, gamma cameras and SPECT have become increasingly important diagnostic tools. These tools have been used to image virtually every organ in the body. Brain tumors, for example, can be located by SPECT after intravenous injection of Na99mTcO4, as brain tumors have a very high affinity for Tc. Alzheimers disease has been studied using a gamma camera and the radioisotope 133Xe. Other radioisotopes and their medical uses include 133Xe/99mTc for pulmonary embolism, 123I/99mTc for renal function, and 201TI for cardiac infarction and ischaemia.
Boron Neutron-Capture Therapy
Boron Neutron Capture Therapy (BNCT) is an experimental approach to cancer treatment that is based on a dual-step technique: accumulation of a boron-containing compound within a tumor and treatment with a beam of low-energy neutrons directed at the boron-containing tumor. The nuclei of the boron atoms capture the neutrons and split into two highly charged particles (alpha particle and lithium ion) that have very short path lengths, approximating one cell diameter. These charged particles release sufficient energy locally to kill any tumor cells that contain high concentrations of boron. Over the past nine years, the United States Dept. of Energy (DOE) has supported a nationwide research program to develop BNCT for clinical use.
Catching Neutrons to Combat Cancer
Subjecting boron atoms to low-energy neutron radiation (thermal neutrons) causes the boron nuclei to disintegrate into alpha particles and lithium isotopes with a kinetic energy of 2.5 MeV. When this disintegration occurs in malignant cells, the energy generated is sufficient to destroy them without damaging the neighboring cells, since the range of the particles is only about 10 microns. In such BNCT, it has been estimated that it takes 109 boron atoms per tumor cell for a therapeutic dose. See Hawthorne et al., J. Neuro-Oncology, (2003) 62: 33-45. As each tumor cell has about 106 effective antigenic sites that can act as targets, the number of boron atoms required per carrier has been calculated to be 103. Thus, 1,000 boron atoms are needed per antibody molecule for effective treatment. However, this has been heretofore impractical because when this many small carbo-borane molecules are attached to the antibody molecule, it loses its tumor-specific targeting ability. Hawthorne et al.
Other boron-containing compounds (e.g., porphyrins containing boron) currently being used in such therapies, however, generally comprise only a very small amount of boron. It would be useful if a molecular species with a higher percentage of boron (wt. % relative to the overall molecular weight of the molecule) could be used in BNCT.
Boron Nitride Nanotubes
Boron nitride (BN) nanotubes have been synthesized and shown to behave in many ways like their carbon nanotube analogues [Chopra et al., Solid State Commun., (1998) 105: 297-300; Cumings et al., Chem. Phys. Lett., (2000) 316: 211-216]. For example, they show the same propensity to agglomerate into bundles held together by van der Waals attractive forces. Furthermore, they have been observed to exist as single- or multi-walled varieties. There are notable differences, however, namely that they are insulating and possess a constant bandgap of 5 eV irrespective of tube diameter, number of walls, and chirality [Demczyk et al., Appl. Phys. Lett., (2001) 78(18): 2772-2774; Mickelson et al., Science, (2003) 300: 467-469].
Use of such BN nanotubes (BNnt), such as those described above, in BNCT would be very advantageous on a percent boron basis—if BN nanotubes could be made therapeutically deliverable. Additionally, other types of nanotubes and nanostructures could be made to serve as delivery vehicles in cancer treatments and in diagnostic imaging. A related advantage is the ability to attach BN nanostructures to an IgG or other targeting biomolecule at only one or a few locations, so that the attached therapeutic atoms do not cover or interfere with the target molecule's receptor and thus compromise specificity.